This project supports a research partnership between two academic institutions and an industrial collaborator to develop and translate a new high-resolution contrast ultrasound modality. Microbubble ultrasound contrast agents can be excited near their resonance to produce very high-frequency broadband content. However, until a recent collaboration between co-investigators Paul Dayton and F. Stuart Foster, transducers with the ultra-wide bandwidth to take advantage of this phenomenon have not existed. In our previous collaboration, we have developed a prototype mechanically-scanned dual-frequency transducer technology which enables contrast agents to be excited near their resonance (2-5 MHz) and their broadband content to be detected between 15-45 MHz. The implementation of this transducer technology has enabled contrast enhanced ultrasound imaging with unprecedented resolution and contrast to noise ratio. The images obtained with this method depict images of microvascular structure and pattern, without background signal from tissue - which is why we now refer to it as """"""""Acoustic Angiography"""""""". Dr. Dayton has furthermore applied this technology in several pre-clinical settings, and demonstrated that Acoustic Angiography has substantial utility in cancer imaging - being able to detect with high sensitivity both vascular density and vascular morphology, biomarkers which are known to correlate with tumor malignancy. Preliminary data has demonstrated that Acoustic Angiography can differentiate healthy from tumor-bearing tissue by assessing the microvascular fingerprint alone. It is thus the goal of this project to further develop this new imaging approach, Acoustic Angiography, and propel its translation both into the clinic and for pre-clinical applications (of which there are mny in oncology research). In order to do this, we need to design a dual frequency linear array ultrasound transducer, and integrate it with a commercial imaging system. Thus, our project is as follows: Co-Investigator Stuart Foster's group, experts in the field of high frequency transducer design as well as general ultrasound imaging, will design the dual frequency array system based on preliminary data from the Dayton group. Industrial collaborators at Visual Sonics, Inc, the world leader in high-frequency ultrasound systems, will utilize their state-of-the art fabrication transducer facilities to construct the transducers. Drs. Dayton and Foster will evaluate the prototypes in vitro and in-vivo, using a custom research (Verasonics) ultrasound system, and provide feedback to Visual Sonics. The prototype transducer will be software and hardware integrated into the Vevo 2100, a commercial high-frequency array based ultrasound system. Finally, the final system will be evaluated in a clinical cancer imaging study at UNC Chapel Hill with clinical collaborators Dr. Lee and Kuzmiak. In summary, this academic-industrial partnership will develop the hardware and software required to translate a promising new ultrasound imaging technology, Acoustic Angiography, to the clinic.
This Academic-Industrial Partnership proposes translation of a new contrast enhanced ultrasound modality which may enable improved biopsy guidance, improved differentiation of indeterminate lesions, improved sensitivity to micro tumors, and assessment of tumor response to therapy prior to volume changes. The project will involve working with industrial collaborators to develop a unique dual-frequency linear array ultrasound probe for transcutaneous high-resolution contrast enhanced ultrasound. This probe will be evaluated preclinically and in patients for cancer imaging applications.
| Lindsey, Brooks D; Shelton, Sarah E; Foster, F Stuart et al. (2017) Assessment of Molecular Acoustic Angiography for Combined Microvascular and Molecular Imaging in Preclinical Tumor Models. Mol Imaging Biol 19:194-202 |
| Lin, Fanglue; Shelton, Sarah E; Espíndola, David et al. (2017) 3-D Ultrasound Localization Microscopy for Identifying Microvascular Morphology Features of Tumor Angiogenesis at a Resolution Beyond the Diffraction Limit of Conventional Ultrasound. Theranostics 7:196-204 |
| Lin, Fanglue; Tsuruta, James K; Rojas, Juan D et al. (2017) Optimizing Sensitivity of Ultrasound Contrast-Enhanced Super-Resolution Imaging by Tailoring Size Distribution of Microbubble Contrast Agent. Ultrasound Med Biol 43:2488-2493 |
| Lindsey, Brooks D; Shelton, Sarah E; Martin, K Heath et al. (2017) High Resolution Ultrasound Superharmonic Perfusion Imaging: In Vivo Feasibility and Quantification of Dynamic Contrast-Enhanced Acoustic Angiography. Ann Biomed Eng 45:939-948 |
